Articles tagged with: Kidney Cancer

Our First Guest Blog for May 2014 is by Dr Shankar Siva, a Radiation Oncologist from The Peter MacCallum Cancer Centre in Melbourne. He discusses the new technique of Sterotactic Ablative Body Radiotherapy for kidney cancer in patients who are not medically fit for surgery. This new approach is still in a study period, but may offer cancer control to patients who do not have other treatment options.

Shankar, can you explain what Stereotactic Ablative Body Radiotherapy (SABR) is, and what advantages it has over other forms of radiotherapy?

Stereotactic ablative body radiotherapy (SABR) is a high precision radiotherapy technique that involves between 1 and 5 treatments. This is very different from conventional radiotherapy that involves daily radiotherapy for up to 8 weeks. It is non-invasive, painless, delivered without any need for anaesthetic, and conveniently does not require in-patient hospitalisation. SABR requires high-tech radiotherapy equipment for safe delivery, such as motion management for the tumour, accurate image guidance, and robust immobilisation. When delivered correctly, SABR can achieve submillimetre accuracy. Because of its precision, the SABR technique allows for much higher biological doses than can be safely delivered using conventional radiotherapy techniques. As such, most studies in sites such as the brain, lung and spine report cancer control rates in the order of 90% or greater after SABR.

Sterotactic radiotherapy for some other types of tumour has been around for some time. Why has it only recently been looked at for kidney tumours?

Stereotactic radiotherapy was first devised for brain tumours by Swedish neurosurgeon Lars Leksell in 1951, who termed it “radiosurgery”, so yes, it has been around for a very long time! Cranial "radiosurgery" was performed by using a rigid frame around the skull which allowed for accurate delivery of the radiation dose. However, tumours in other organs such as the lung, liver, and kidney are all highly mobile due to normal breathing or from the pumping of the heart. Only recently have technological advances allowed us to account for and manage tumour motion during radiotherapy delivery. The kidney in particular is a challenging organ, as it is quite mobile and surrounded by many sensitive organs.

Which group of patients is likely to be suitable for this treatment for kidney tumours?

Surgery is still the standard of care for patients with kidney cancer. However, kidney cancer is typically a disease of the older population, with the average age of diagnosis being 65 years of age. Some patients have other medical conditions which make invasive procedures potentially risky, particularly those patients who may have significant pre-existing kidney dysfunction, are risky anaesthetic candidates, or have heart disease and are reliant on blood thinners. In light of this risk, other procedures such as SABR and radiofrequency or microwave ablation have emerged as treatment alternatives for inoperable patients. In contrast to SABR, the disadvantage of radiofrequency ablation and microwave ablation is that those techniques can typically treat only treat smaller tumours, require the insertion of electrodes through the skin into the kidney (invasive), and are not as effective when tumours are close to blood vessels. On the other hand, the disadvantage of SABR is that it is typically restricted to patients who have not previously received radiotherapy to the upper abdomen. Otherwise, we expect that most patients who are not suitable for surgery on medical grounds may be eligible for treatment using the SABR technique.

What are the potential side effects?

In the early period after treatment, we expect that most patients feel tired. There may be some nausea, or loose bowel actions. Some patients may experience some reflux or heartburn. We typically prescribe preventative medications to help with these side effects. There may be a mild skin reaction, similar to a very light sunburn, particularly around the back. These side effects usually resolve within the first 2-3 weeks, and we expect all of these side effects to be resolved by around 6 weeks post treatment. The longer term effects of SABR in the kidney are less well understood. There is a potential for decline in kidney function, rise in blood pressure, scarring or narrowing of the bowel, or very rarely ulceration of the bowel or stomach. To date, studies have shown that the risk of severe side effects to be less than 5%.

This treatment is currently part of a study at the Peter Mac. What do you think the future holds for this treatment for kidney tumours?

We have pioneered this technique in Australia through the FASTRACK clinical trial, one of the few clinical trials using SABR for localised kidney cancer in the world. This study is expected to be complete later in 2014, and to date the results have been very promising. We would like to make this treatment accessible to all patients in Australia. However, the problem is that technology is very complex and varies from centre to centre. The Peter Mac is one of the largest radiation oncology institutions in the southern hemisphere and an Australian leader in the SABR technique, so we are not certain whether our results can be immediately reproduced in other institutions across Australia.

The next phase in our research program is to lead a multicentre study of SABR for kidney cancer involving multiple cancer centres across Australia. All the treatment plans will be centrally reviewed by our team at the Peter Mac for quality assurance, in order for this new treatment to be safely introduced across Australia. If this study is successful, I imagine that stereotactic radiotherapy will become a readily available treatment alternative for inoperable patients with primary kidney cancer.

Dr Siva is a Radiation Oncologist, Research Staff Specialist and NHMRC Scholar at the Peter MacCallum Cancer Centre in Melbourne. His major research interests are in high-tech radiation delivery and radiation biology. He is the lead clinician of the stereotactic body radiotherapy program at the Peter MacCallum Cancer Centre, and coordinates the first dedicated Stereotactic Ablative Body Radiotherapy (SABR) clinic in Australia. He published the first original research using the SABR technique in Australia. He serves on the Radiation Oncology Research Committee (RORC) of the Royal Australian and New Zealand College of Radiologists, on the renal subcommittee of the Australian and New Zealand Urogenital and Prostate (ANZUP) trials group, and as the radiation oncologist on the Management Advisory Committee (MAC) of the Australasian Lung Cancer Trials Group (ALTG). He is the principal investigator of multiple radiotherapy clinical trials of SABR in the context of lung, kidney and prostate malignancies.

David Nicol is a Consultant Urological Surgeon at the Royal Marsden Hospital in London where he is also Chief of Surgery. His clinical work deals with complex kidney and testis cancer including surgery in patients with advanced and metastatic disease. Here, he explains the use of cytoreductive nephrectomy in metastatic kidney cancer.

David, can you explain what is meant by cytoreductive nephrectomy?

Cytoreductive nephrectomy refers to the removal of the primary kidney tumour in patients who have metastatic disease. Historically it had been noted that occasional patients experienced spontaneous regression of metastatic disease when this was performed. This however only occurred in a very small number of cases and general opinion was that cytoreductive nephrectomy as the overwhelming majority died within 12-18 months from metastatic disease. In the late 1980’s and early 1990’s, drugs which stimulated the immune system(immunotherapy) had an effect on metastatic kidney cancer.

Small trials with 2 agents interferon-alpha (IFN-a) and interleukin-2 (IL-2) showed response rates better than what had been observed with conventional cytotoxic chemotherapy. Analysis of these studies suggested that patients who had a nephrectomy performed prior to treatment resulted in a better response to both INF-a and IL-2. The basis for this was uncertain with possibilities including a selection bias with only fitter patients, who would otherwise expect to live longer, having nephrectomy. Alternatively it was also proposed that cytoreductive nephrectomy may exert some biological effect improving the effectiveness of immunotherapy and thus overall survival.

Which patients with metastatic kidney cancer are suitable for cytoreductive nephrectomy?

Cytoreductive nephrectomy is really only an appropriate option for patients who are otherwise well. Patients whose performance status is impaired are at high risk of complications from major surgery and also generally have poor survival that is not improved with cytoreductive nephrectomy. Therefore patients who have noted significant weight loss, are anemic or who feel tired and generally unwell are not considered candidates for cytoreductive nephrectomy. Some patients may present with significant symptoms including pain and bleeding for which nephrectomy is recommended. This is regarded as a palliative intervention to control symptoms rather than a cytoreductive nephrectomy which is performed with the expectation that it may improve survival.

Can you outline the evidence that cytoreductive nephrectomy can be beneficial in some patients?

There are 2 trials – one performed in Europe and another in the United States that have demonstrated a survival benefit with cytoreductive nephrectomy in patients who are subsequently treated with IFN-a. These were both randomised controlled trials - in which patients, who all received IFN-a were randomly allocated to either cytoreductive nephrectomy or no surgery. Comparing the 2 groups which were of equal size revealed that patients undergoing cytoreductive nephrectomy had a median survival of 14 months compared to 8 months without. These studies also reinforced the lack of benefit in patients with poor performance status.

This is obviously difficult surgery. Are complication rates much higher compared to other forms of kidney cancer surgery?

Patients with metastatic kidney cancer usually have quite large primary tumours with a rich blood supply being a common feature. Both of these factors can make surgery very difficult and associated with a higher risk of complications, particularly major bleeding, compared to other forms of kidney cancer surgery. Most patients with kidney cancer have relatively small tumours and are able to have surgery performed either laparoscopically or robotically with low risk of complications. In contrast cytoreductive nephrectomy, in almost all cases, requires major open surgery as minimally invasive procedures are usually neither feasible nor safe. Patients with metastatic cancer are also generally at higher risk of complications with major surgery. Deep venous thrombosis and pulmonary embolism are 2 specific examples of this.

A relatively new treatment for metastatic kidney cancer is a class of drugs called tyrosine kinase inhibitors (TKIs). Is there any evidence that cytoreductive nephrectomy followed with TKIs is beneficial for patient outcomes and survival?

The treatment of metastatic kidney cancer has rapidly changed and now IFN-a and IL-2 are rarely used. Both agents have been largely replaced by a new group of drugs – termed targeted therapies due to their effect as tyrosine kinase inhibitors (TKIs). These drugs have a completely different mechanism of action – rather than stimulating the immune system they target tumour blood vessels. Essentially they reduce the blood flow to tumours.

At this point in time it is unknown whether or not cytoreductive nephrectomy improves the outcome in patients treated with TKI’s. It is important to note that the previous studies on cytoreductive nephrectomy only addressed the question as to whether or not this improved survival when patients were treated with IFN-2. Accepting the lack of clear evidence at this time it can still be considered in some patients. For example a patient who is otherwise well presenting with a kidney cancer and small volume metastatic disease I would suggest a cytoreductive nephrectomy as their initial management. The patient would then be observed, avoiding drug treatment until they show clear evidence of substantial progression of their metastatic disease. The rationale behind this is that TKI’s can have significant toxicity and also that resistance to treatment inevitably develops. By removing the kidney and delaying drug therapy the patient avoids toxicity of treatment and also emergence of resistance at a time when their metastatic disease may be stable or only slowly progressing(ie reserving it for maximum effect when it is really needed).

A different approach to cytoreductive nephrectomy would be considered in the patient with high volume or symptomatic metastatic disease. In this scenario I would not recommend cytoreductive nephrectomy as an initial step. Rather the patient should consider commencing a TKI from the outset. Surgery could delay therapy during which time his disease may progress with an overall deterioration in his condition such that he is never suitable for a TKI (as again these drugs only appear of benefit in patients with good performance status).

Alexander Kutikov, MD is a Surgical Oncologist and Associate Professor of Urologic Oncology at the Fox Chase Cancer Center in Philadelphia. He is a highly published author and experienced presenter on the topic of Urological Cancer, and is very active in Social Media in Urology. In this Guest Post, Alex gives a concise account of the diagnosis and treatment options for localised kidney cancer. He explains what you need to know, and what you should ask your surgeon.

"If you or your loved one has been diagnosed with a kidney tumor / mass, reliable information regarding this condition is often difficult to obtain. It is important that you have a good understanding of the diagnostic and treatment options available in order to make an educated choice on how to best proceed with your treatment.

"Generally, when patients are diagnosed with a kidney mass, it is apparent on imaging studies whether the tumor is localized to the kidney or if it has spread beyond the kidney to other parts of the body. For patients with localized disease, surgical resection remains the gold standard, and is largely superior to therapies such as cryotherapy or radiofrequency ablation.

"The following points are important to remember:

1. Understand that not All Kidney Tumors are Malignant.

Approximately 15-20% of newly diagnosed localized kidney masses are benign. Such lesions - largely complex cysts, oncocytomas, and angiomyolipomas - are often indistinguishable from kidney cancer with modern imaging. However, at times, expert radiologists are able to review a patient's imaging study and make a diagnosis of a benign lesion, saving an individual from unnecessary treatment.

A percutaneous biopsy performed under expert radiographic guidance and interpreted by experienced pathologists can sometimes provide valuable information to guide treatment decisions in select cases.

Tertiary treatment goal: Utilization of minimally invasive surgical approaches - . Both transperitoneal and retroperitoneal minimally-invasive (laparoscopic / robotic) surgical approaches are currently utilized by expert kidney surgeons. Finding the right surgeon may help avoid a large painful incision, albeit traditional open kidney surgery continues to play an important role in management of some patients with large / anatomically complex kidney tumors.

3. Be Prepared During Your Visit.

Here are some questions to pose to your treating physician when you or your family member is diagnosed with a renal mass:

Understand characteristics of your mass: size of tumor, clinical stage of tumor, RENAL nephrometry score. If your tumor has been resected, be sure to obtain information regarding pathologic stage, grade and histology. Pathology review by expert pathologists at times can make a critical difference in guiding further treatments.

radical nephrectomy: if radical nephrectomy is offered, be sure to establish that partial nephrectomy is not possible at a more experienced center. If kidney preservation is not possible, can radical nephrectomy be performed with minimally-invasive techniques?

Risks of treatment: be sure to understand risks associated with each option.

"In summary, kidney cancer is curable in the majority of cases and its treatment is rapidly evolving. Finding an expert urologic surgeon who not only understands this complex disease, but also possesses the needed surgical skills to appropriately manage this condition is critical to successful outcomes."

Continuing the series of Guest Posts by highly regarded Urologists, Benjamin Davies from UPMC answers questions on Urologic Cancer Surgery

Dr. Benjamin Davies is a Urological Surgeon specialising in cancer management. He is an Assistant Professor in Urology at the University of Pittsburgh Medical Centre and the Director of the Urologic Oncology Fellowship. He is a respected clinician scientist and is considered a pioneer for urologists in social media, particularly Twitter.

In this post, Ben Davies answers questions on the current practice and future development of urological cancer surgery

Ben, what was your motivation to concentrate on urology cancers?

I think I was frankly attracted to tumour biology first and then I was introduced to the actual surgery. Once I started being a surgeon I quickly forgot about the basic science biology and become engrossed in large cancer surgeries and robotically enhanced ones as well. I like the direct impactful role that surgery offers to the patient right then and there. No waiting for medication to work or waiting for lab work….it’s operate and hopefully cure. Concrete work.

What is the hardest part of your job?

Sick patients are the absolutely most challenging. It’s simply not a 9-5 job. When I have a patient that is struggling I tend to really take it personally (which of course you shouldn’t) and you can easily become very stressed. Learning to manage the stress is part of becoming a successful physician but is definitely the most challenging.

What have been the biggest developments in urologic cancer in the past few years?

I think two things are the biggest developments:

1. Robotic surgery has significantly aided our surgical approach to prostate cancer care. It has without a doubt decreased the side effect profile of a rather morbid procedure.

2. Genomic testing is finally coming online. We have all been waiting for real genomic testing to help us with our care and the new prostate cancer tests (while still at the beginning of their testing) are promising.

What is the most important preventative measure in urological cancer?

Do not smoke. It is an absolute tragedy to smoke. Just stop it.

Ten years ago, an old boss of mine said to me …”Brook, in years to come you will look back on a holocaust of radical prostatectomies.” Is there is any truth in this?

Of course he was right!! We have done a major disservice in over-treating prostate cancer patients. And as a result our large US screening studies are flawed and we now have to deal with the consequences of bad data. The PSA screening debate has turned against us because we over-treated low volume, low risk prostate cancer without any pause and many times just for money. Hopefully the new generation of urologists has been sufficiently educated to stop the nonsense.

In ten years time, what will prostate cancer treatment look like?

Easy. After your MRI-guided biopsy you will get a genomic profile and risk stratification of your disease. If you are healthy man, then you will be offered a robotic prostatectomy at a centre of excellence.

Prostate cancer receives a huge amount of publicity and funding. Which urology cancer gets a rough deal, and what can be done to improve this?

The absolute worst is bladder cancer! The patient population that is affected is older, sicker, and has lower socioeconomic means. What to do?? The Bladder Cancer Advocacy Network is beginning to generate better lobbying efforts and academics certainly need to bring this issue to the fore more often.

The early symptoms of bladder and kidney cancer may be harder to detect in women than in men, a recent study suggests.

The study from the journal BMJ Open revealed that women in the UK diagnosed with kidney or bladder cancer were twice as likely as men to have visited their GP three or more times before they were referred to a specialist.

This is probably because the symptoms associated with benign conditions such as urinary tract infection (cystitis) can be similar, and UTI/cystitis is much more common in women than men. Men rarely get UTIs, so it is easier to establish that blood in the urine is related to something other than a UTI.

The principal trigger for referral is blood in the urine, detected on a urine test. The difficulty is that blood is often present when the patient has a UTI, and in this setting, blood does not necessarily indicate anything sinister. If blood persists after an infection is treated, further investigation may be needed.

If a UTI is present along with blood in the urine (on a lab test), the UTI should be treated, and the urine re-tested after treatment. If blood is still present, a urological referral is usually made.

If you actually see blood in your urine at any time, you must let your GP know straight away.